Single Holliday Junctions Are Intermediates of Meiotic Recombination

Abstract

Crossing-over between homologous chromosomes facilitates their accurate segregation at the first division of meiosis. Current models for crossing-over invoke an intermediate in which homologs are connected by two crossed-strand structures called Holliday junctions. Such double Holliday junctions are a prominent intermediate in Saccharomyces cerevisiae meiosis, where they form preferentially between homologs rather than between sister chromatids. In sharp contrast, we find that single Holliday junctions are the predominant intermediate in Schizosaccharomyces pombe meiosis. Furthermore, these single Holliday junctions arise preferentially between sister chromatids rather than between homologs. We show that Mus81 is required for Holliday junction resolution, providing further in vivo evidence that the structure-specific endonuclease Mus81-Eme1 is a Holliday junction resolvase. To reconcile these observations, we present a unifying recombination model applicable for both meiosis and mitosis in which single Holliday junctions arise from single- or double-strand breaks, lesions postulated by previous models to initiate recombination.

Human SLX4 Is a Holliday Junction Resolvase Subunit that Binds Multiple DNA Repair/Recombination Endonucleases

“…It appears that meiotic crossing-over (CO) relies on different endonucleases in differents organisms. While flies rely essentially on MEI9 XPF (Yildiz et al, 2002) and fission yeast on Mus81 Cromie et al, 2006), crossing-over in budding yeast appears to rely on multiple pathways (Hollingsworth and Brill, 2004). Interestingly, large scale transcriptome studies show that the highest SLX4 mRNA levels in mouse tissues are in testes, oocytes and fertilized eggs (Su et al, 2002), consistent with the idea that SLX4 is involved in meiotic recombination in mammals.…”

Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis

“…In ZMM mutants the remaining CO do not show interference as measured genetically, and most depend on Mus81/Mms4 (De Los Santos et al 2003). Interestingly, in S. pombe, where CO do not show interference, CO are completely dependent on Mus81/Eme1 (the S. pombe homolog of Mus81/ Mms4) and go through a single Holliday junction intermediate (Hollingsworth & Brill 2004, Cromie et al 2006. One current major issue is to understand how the decision for CO/NCO is made (Borner et al 2004, Bishop & Zickler 2004 and how the proper number and position of CO are achieved in each meiotic cell.…”

The double life of Holliday junctions

“…Both events can originate from the asymmetric cleavage of single HJs [1,2] or even double HJs [3]. Double HJs and single HJs have been visualized in the yeasts S. cerevisiae and S. pombe during meiotic DSB repair [2,4]. Yet, a key question is whether HJs are also the DNA intermediates used in DNA break repair during the mitotic cell cycle.…”

“…In a single recombination event, gene conversion is frequently associated with crossovers (a reciprocal exchange of flanking markers). Both events can originate from the asymmetric cleavage of single HJs [1,2] or even double HJs [3]. Double HJs and single HJs have been visualized in the yeasts S. cerevisiae and S. pombe during meiotic DSB repair [2,4].…”